A number of pathological conditions, illustratively including acne, rosacea, psoriasis, promyelocytic leukemia and neuroblastoma, are currently treated using retinoids and are considered retinoid-responsive conditions.
For example, acne is the most prevalent skin condition encountered by dermatologists, affecting nearly 85% of the people between the ages of 12 and 24 years (15). While acne is not life-threatening, it does have significant physical and psychosocial morbidity (16). Acne results from the interplay of 4 factors: increased production sebum by the sebaceous gland, altered keratinization of follicular keratinocytes, activity of Propionibacterium acnes (P. acnes) and inflammation. P. acnes contributes to the inflammation associated with acne via activation of Toll-like receptor 2 on the surface of inflammatory cells in the skin infiltrate (17).
Isotretinoin (13-cis RA) is the most potent agent that affects all the pathogenic features of acne. It is the only therapeutic agent that drastically reduces the size and secretion of sebaceous glands. However, isotretinoin, like thalidomide, is a teratogen and its use is closely regulated through an FDA-mandated risk management program called iPLEDGE.
There is a continuing need for methods and compositions to treat retinoid-responsive conditions.